tbuckley/cabot-search huggingface dataset:
Activation of the cGAS/STING Axis in Genome-Damaged Hematopoietic Cells Does Not Impact Blood Cell Formation or Leukemogenesis
Authors: Nicole Dressel, Loreen Natusch, Clara M. Munz, Santiago Costas Ramon, Mina N.F. Morcos, Anja Loff, Björn Hiller, Christa Haase, Livia Schulze, Patrick Müller, Mathias Lesche, Andreas Dahl, Hella Luksch, Angela Rösen-Wolff, Axel Roers, Rayk Behrendt, Alexander Gerbaulet
Journal: Cancer Research (2023)

Genome damage is a main driver of malignant transformation, but it also induces aberrant inflammation via the cGAS/STING DNA-sensing pathway. Activation of cGAS/STING can trigger cell death and senescence, thereby potentially eliminating genome-damaged cells and preventing against malignant transformation. Here, we report that defective ribonucleotide excision repair (RER) in the hematopoietic system caused genome instability with concomitant activation of the cGAS/STING axis and compromised hematopoietic stem cell function, ultimately resulting in leukemogenesis. Additional inactivation of cGAS, STING, or type I IFN signaling, however, had no detectable effect on blood cell generation and leukemia development in RER-deficient hematopoietic cells. In wild-type mice, hematopoiesis under steady-state conditions and in response to genome damage was not affected by loss of cGAS. Together, these data challenge a role of the cGAS/STING pathway in protecting the hematopoietic system against DNA damage and leukemic transformation.Loss of cGAS/STING signaling does not impact DNA damage-driven leukemogenesis or alter steady-state, perturbed or malignant hematopoiesis, indicating that the cGAS/STING axis is not a crucial antioncogenic mechanism in the hematopoietic system. See related commentary by Zierhut, p. 2807.
Evolving trends and outcomes in older patients with acute myeloid leukemia including allogeneic stem cell transplantation
Authors: Alexandre Bazinet, Hagop Kantarjian, Naszrin Arani, Uday Popat, Alex Bataller, Koji Sasaki, Courtney D. DiNardo, Naval Daver, Musa Yilmaz, Hussein A. Abbas, Nicholas J. Short, Ghayas Issa, Elias Jabbour, Sherry A. Pierce, Julianne Chen, Ricky Garcia, Marina Konopleva, Guillermo Garcia‐Manero, Amin Alousi, Elizabeth J. Shpall, Richard E. Champlin, Gautam Borthakur, Farhad Ravandi, Tapan Kadia
Journal: American Journal of Hematology (2023)

Abstract Outcomes in older patients with acute myeloid leukemia (AML) have historically been poor. Given advances in low‐intensity therapy (LIT) and stem cell transplantation (SCT), we performed a retrospective single‐center study to evaluate the contemporary outcomes of this population. We reviewed all patients ≥60 years with newly diagnosed AML between 2012 and 2021 and analyzed treatment and SCT‐related trends and outcomes. We identified 1073 patients with a median age of 71 years. Adverse clinical and cytomolecular findings were frequent within this cohort. In total, 16% of patients were treated with intensive chemotherapy, 51% with LIT alone, and 32% with LIT plus venetoclax. The composite complete remission rate with LIT plus venetoclax was 72%, which was higher than with LIT alone (48%, p &lt; .0001) and comparable to intensive chemotherapy (74%, p = .6). The median overall survival (OS) with intensive chemotherapy, LIT, and LIT plus venetoclax was 20.1, 8.9, and 12.1 months, respectively. 18% of patients received SCT. SCT rates were 37%, 10%, and 22% in patients treated with intensive chemotherapy, LIT, and LIT plus venetoclax, respectively. The 2‐year OS, relapse‐free survival (RFS), cumulative incidence (CI) of relapse, and CI of treatment‐related mortality with frontline SCT ( n = 139) were 59%, 52%, 27%, and 22%, respectively. By landmark analysis, patients undergoing frontline SCT had superior OS (median 39.6 vs. 21.4 months, p &lt; .0001) and RFS (30.9 vs. 12.1 months, p &lt; .0001) compared with responding patients who did not. Outcomes in older patients with AML are improving with more effective LIT. Measures should be pursued to increase access to SCT in older patients.
Multimorbidity: small steps in the right direction
Authors: Adewale O Adebajo
Journal: BMJ (2023)

Richards gives a voice to millions of patients, both in the UK and across the world. 1 There seems to be-fortunately-a growing realisation that things cannot continue in this way.In the UK, integration of services is being mandated in both health and social care.Many healthcare professionals-care of the elderly physicians in particular-are rising to the challenge of providing truly holistic care.In addition, specialties like my own are ensuring that their trainees acquire the knowledge and skills of general internal medicine alongside specialty and subspecialty training, to provide more joined up care.Despite initial resistance from some parts of the profession, internal medicine subspecialties now require trainees to have sufficient general internal medicine training to be able to participate in on-call rotas at specialist registrar level.There is also good news with regard to a similar joined up approach for research into multiple long term conditions.For too long, researchers have adopted a siloed approach to researching chronic conditions.The National Institute for Health and Care Research (NIHR) has listened to the views of patients, however, and has recently funded a "multiple long term conditions" research stream.Although there are concerns that this could lead to a reduction of research funding into individual conditions, so far there is no indication that this will happen.Furthermore, the programme includes public contributors in the prioritisation phase.Part of the ongoing makeover of multimorbidity has been replacement of the term with "multiple long term conditions," following patient feedback.These are all small steps, but in the right direction.Ultimately, the hope is that the matters that Richards and millions of other patients have and continue to raise about multiple long term conditions are at last being tackled.
Approach to vaccination in systemic lupus erythematosus on biological treatment
Authors: Reşit Yıldırım, Tatiana Oliveira, David Alan Isenberg
Journal: Annals of the Rheumatic Diseases (2023)

In recent years, treat-to-target strategy and early intervention strategies with immunosuppressive agents have attempted to improve the prognosis and outcome in patients with autoimmune inflammatory rheumatic diseases. However, infectious complications due to side effects of medication remain a major concern in routine practice. In this regard, vaccine immunity and vaccination programmes are of the utmost importance in patients with systemic lupus erythematosus (SLE) in terms of morbidity and mortality. Encouragingly, research investigations have increased exponentially, both in monitoring the vaccines efficacy, and in determining the immune response while patients are on immunosuppression., However, in this biological era in rheumatology, relatively little data have been published investigating these parameters in those receiving biological agents, therefore, no definitive consensus about a vaccination policy for patients with SLE is currently available. In this review, we aim to address what is established about vaccinating patients with SLE on biological agents and discuss potential problems.
Disaster waste management after earthquakes: lessons from Turkey and Syria
Authors: Sevilcan Başak Ünal, Cavit Işık Yavuz
Journal: BMJ (2023)

Pre-prepared and specialised disaster waste management is essential to avoiding environmental health and safety problems after natural disasters, write <b>Sevilcan Başak Ünal</b> and <b>Cavit Işık Yavuz</b>
Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium
Authors: Davide Capodanno, Roxana Mehran, Mitchell W. Krucoff, Usman Baber, Deepak L. Bhatt, Piera Capranzano, Jean-Philippe Collet, Thomas Cuisset, Giuseppe De Luca, Leonardo De Luca, Andrew Farb, Francesco Franchi, C. Michael Gibson, Joo-Yong Hahn, Myeong-Ki Hong, Stefan James, Adnan Kastrati, Takeshi Kimura, Pedro A. Lemos, Renato D. Lopes, Adrian Magee, Ryosuke Matsumura, Shuichi Mochizuki, Michelle L. O’Donoghue, Naveen L. Pereira, Sunil V. Rao, Fabiana Rollini, Yuko Shirai, Dirk Sibbing, Peter C. Smits, P. Gabriel Steg, Robert F. Storey, Jurrien ten Berg, Marco Valgimigli, Pascal Vranckx, Hirotoshi Watanabe, Stephan Windecker, Patrick W. Serruys, Robert W. Yeh, Marie-Claude Morice, Dominick J. Angiolillo
Journal: Circulation (2023)

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.
Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial
Authors: Yiwen Ling, Li Xuan, Na Xu, Fen Huang, Zhiping Fan, Ziwen Guo, Xiaojun Xu, Hui Liu, Ren Lin, Sijian Yu, Haiyan Zhang, Hua Jin, Meiqing Wu, Can Liu, Xinquan Liang, Ruiming Ou, Yuping Zhang, Xiaodan Liu, Hong Qu, Xiao Zhai, Jing Sun, Ying Zhao, Qifa Liu
Journal: Journal of Clinical Oncology (2023)

The busulfan plus fludarabine (BuFlu) conditioning regimen has lower transplant-related mortality (TRM) than busulfan plus cyclophosphamide (BuCy) in HLA-matched transplantation. We aimed to compare outcomes of the BuFlu regimen with those of the BuCy regimen in HLA-haploidentical hematopoietic cell transplantation (haplo-HCT).
Long-term survival after female pelvic organ-sparing radical cystectomy versus standard radical cystectomy: a multi-institutional propensity score-matched analysis
Authors: Wenlong Zhong, Kun Xia, Libo Liu, Sida Cheng, Hong Peng, Wang He, Wen Dong, Hao Liu, Yiming Lai, Hao Han, Cheng Liu, Hongxian Zhang, Xinfei Li, Guangpu Ding, Xuesong Li, Lulin Ma, Liqun Zhou, Tianxin Lin, Jian Huang
Journal: International Journal of Surgery (2023)

The application of pelvic organ preserving-radical cystectomy (POPRC) in female patients with bladder cancer has attracted more and more attention in recent years. In the current study, the authors aim to compare the long-term oncological outcomes of POPRC versus standard radical cystectomy (SRC) in a large multicenter retrospective cohort.Data on female patients with bladder cancer who underwent POPRC or SRC in January 2006 and April 2018 were included from three Chinese urological centers. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival and recurrence-free survival. To decrease the effect of unmeasured confounders associated with treatment selection, 1:1 propensity score matching was performed.Among the 273 enrolled patients, 158 underwent POPRC (57.9%), and 115 underwent SRC (42.1%). The median follow-up time was 38.6 (15.9-62.5) months. After propensity score matching, each cohort included 99 matched patients. The OS ( P =0.940), cancer-specific survival ( P =0.957), and recurrence-free survival ( P =0.476) did not differ significantly from the two matched cohorts. Subgroup analysis confirmed that the OS was similar between the patients treated with POPRC and SRC across all subgroups examined (all P > 0.05). In multivariable analysis, the surgical method (SRC vs. POPRC) was not an independent risk factor for OS (Hazard ratio 0.874, 95% CI 0.592-1.290; P =0.498).The results showed that no significant difference in long-term survival was determined between female patients undergoing SRC and those undergoing POPRC.
The Prevalence of Polyneuropathy in Type 2 Diabetes Subgroups Based on HOMA2 Indices of β-Cell Function and Insulin Sensitivity
Authors: Frederik Pagh Bredahl Kristensen, Diana Hedevang Christensen, Brian Christopher Callaghan, Jacob Volmer Stidsen, Jens Steen Nielsen, Kurt Højlund, Henning Beck-Nielsen, Troels Staehelin Jensen, Henning Andersen, Peter Vestergaard, Niels Jessen, Michael Hecht Olsen, Torben Hansen, Charlotte Brøns, Allan Vaag, Henrik Toft Sørensen, Reimar Wernich Thomsen
Journal: Diabetes Care (2023)

OBJECTIVE Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of β-cell function and insulin sensitivity. RESEARCH DESIGN AND METHODS We estimated β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S. RESULTS A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15–1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S. CONCLUSIONS Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.
Excess pancreatic elastase alters acinar-β cell communication by impairing the mechano-signaling and the PAR2 pathways
Authors: Giorgio Basile, Amedeo Vetere, Jiang Hu, Oluwaseun Ijaduola, Yi Zhang, Ka-Cheuk Liu, Amira M. Eltony, Dario F. De Jesus, Kazuki Fukuda, Grace Doherty, Colin A. Leech, Oleg G. Chepurny, George G. Holz, Seok-Hyun Yun, Olov Andersson, Amit Choudhary, Bridget K. Wagner, Rohit N. Kulkarni
Journal: Cell Metabolism (2023)
Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification
Authors: Ji Tu, Wentian Li, Philip M. Hansbro, Qi Yan, Xupeng Bai, Chantal Donovan, Richard Y. Kim, Izabela Galvao, Abhirup Das, Cao Yang, Jun Zou, Ashish Diwan
Journal: Molecular Therapy (2023)

Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations and the mechanisms of action remain unclear. We have shown that excessive activation of mast cells (MCs) and their proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, and lung cancer. Previous studies have also shown that MCs and their proteases induce degenerative musculoskeletal disease. By using a custom-designed smoke-exposure mouse system, we demonstrated that CS results in intervertebral disc (IVD) degeneration and release of MC-restricted tetramer tryptases (TTs) in the IVDs. TTs were found to regulate the expression of methyltransferase 14 (METTL14) at the epigenetic level by inducing N6-methyladenosine (m
Thrombus Burden and Outcomes in Patients With COVID-19 Presenting With STEMI Across the Pandemic
Authors: Krishnaraj S. Rathod, Zhi Teoh, Angelos Tyrlis, Fizzah A. Choudry, Stephen M. Hamshere, Katrina Comer, Oliver Guttmann, Ajay K. Jain, Muhiddin A. Ozkor, Andrew Wragg, R. Andrew Archbold, Andreas Baumbach, Anthony Mathur, Daniel A. Jones
Journal: Journal of the American College of Cardiology (2023)
Pulmonary Complications in Patients With Fontan Circulation
Authors: Ali Abdulkarim, Shawn Shaji, Mahmud Elfituri, Megan Gunsaulus, Muhammad A. Zafar, Ali N. Zaidi, Robert H. Pass, Brian Feingold, Geoffrey Kurland, Jacqueline Kreutzer, Rod Ghassemzadeh, Bryan Goldstein, Shawn West, Tarek Alsaied
Journal: Journal of the American College of Cardiology (2023)
Risk of congenital malformation after first trimester mRNA COVID-19 vaccine exposure in pregnancy: the COVI-PREG prospective cohort
Authors: Guillaume Favre, Emeline Maisonneuve, Léo Pomar, Charlotte Daire, Cécile Monod, Begoña Martinez de Tejada, Thibaud Quibel, Monya Todesco-Bernasconi, Loïc Sentilhes, Carolin Blume, Andrea Papadia, Stephanie Sturm, Dirk Bassler, Claudia Grawe, Anda Petronela Radan, Marie-Claude Rossier, Jérôme Mathis, Romina Capoccia-Brugger, Karine Lepigeon, Eva Gerbier, Marie Claude Addor, Ursula Winterfeld, David Baud, Alice Panchaud, Irene Hoesli, Sonia Campelo, Véronique Othenin-Girard, Mirjam Moser, Amaury Brot, Alizée Froeliger, Clémence Houssin, Stylianos Kalimeris, Maria Luisa Gasparri M, Antonilli Morena, Christian Polli, Edoardo Taddei, Daniel Surbek, Luigi Raio, Edouard Ha, Caroline Eggemann
Journal: Clinical Microbiology and Infection (2023)
Effect of SGLT2 Inhibitors on Cardiovascular Outcomes Across Various Patient Populations
Authors: Muhammad Shariq Usman, Tariq Jamal Siddiqi, Stefan D. Anker, George L. Bakris, Deepak L. Bhatt, Gerasimos Filippatos, Gregg C. Fonarow, Stephen J. Greene, James L. Januzzi, Muhammad Shahzeb Khan, Mikhail N. Kosiborod, Darren K. McGuire, Ileana L. Piña, Julio Rosenstock, Muthiah Vaduganathan, Subodh Verma, Shelley Zieroth, Javed Butler
Journal: Journal of the American College of Cardiology (2023)
Performance measurement part I: Foundational knowledge for measure development
Authors: Tatiana Abrantes, Dillon Imbriano, Daniella Reimann, Janet Sullivan, Oliver Wisco, Stephanie Chan, Christopher DiMarco, Nicole Gehret, Nicole Grenier, Paul Imbriano, Benjamin Kahn, Leonardo Lizbinski, Cathy Massoud, Nicole Negbenebor, Sylvia Parra, Deven Patel, Margo Reeder, Allison Robbins, Junko Takeshita, Eric J. Yang, Stephanie C. Braxton, Dirk Elston
Journal: Journal of the American Academy of Dermatology (2023)
Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial
Authors: Ivan T Lee, Catherine A Cosgrove, Patrick Moore, Claire Bethune, Rhiannon Nally, Marcin Bula, Philip A Kalra, Rebecca Clark, Paul I Dargan, Marta Boffito, Ray Sheridan, Ed Moran, Thomas C Darton, Fiona Burns, Dinesh Saralaya, Christopher J A Duncan, Patrick J Lillie, Alberto San Francisco Ramos, Eva P Galiza, Paul T Heath, Bethany Girard, Christy Parker, Dondi Rust, Shraddha Mehta, Elizabeth de Windt, Andrea Sutherland, Joanne E Tomassini, Frank J Dutko, Spyros Chalkias, Weiping Deng, Xing Chen, Jing Feng, LaRee Tracy, Honghong Zhou, Jacqueline M Miller, Rituparna Das, Claire Bethune, Marta Boffito, Duncan Browne, Marcin Bula, Fiona Burns, David Chadwick, Rebecca Clark, Catherine A. Cosgrove, Paul I. Dargan, Thomas C. Darton, Christopher J.A. Duncan, Stevan Emmett, Eva P. Galiza, James Galloway, Paul T. Heath, Lucy Jones, Philip A. Kalra, Rachel Kaminski, Rajeka Lazarus, Patrick J. Lillie, Patrick Moore, Ed Moran, Rhiannon Nally, Adrian Palfreeman, Alberto San Francisco Ramos, Tommy Rampling, Anju Sahdev, Dinesh Saralaya, Ray Sheridan, Roy Soiza
Journal: The Lancet Infectious Diseases (2023)
Successful treatment of JAK1-associated inflammatory disease
Authors: Antoine Fayand, Véronique Hentgen, Céline Posseme, Carole Lacout, Capucine Picard, Philippe Moguelet, Margaux Cescato, Nabiha Sbeih, Thomas R.J. Moreau, Yixiang Y.J. Zhu, Jean-Luc Charuel, Aurélien Corneau, Joelle Deibener-Kaminsky, Stéphanie Dupuy, Mathieu Fusaro, Benedicte Hoareau, Alain Hovnanian, Vincent Langlois, Laurent Le Corre, Thiago T. Maciel, Snaigune Miskinyte, Makoto Miyara, Thomas Moulinet, Magali Perret, Marie Hélène Schuhmacher, Rachel Rignault-Bricard, Sébastien Viel, Angélique Vinit, Angèle Soria, Darragh Duffy, Jean-Marie Launay, Jacques Callebert, Jean Philippe Herbeuval, Mathieu P. Rodero, Sophie Georgin-Lavialle
Journal: Journal of Allergy and Clinical Immunology (2023)
431 Assessment of racial and ethnic differences of atopic dermatitis severity and treatment patterns in a diverse outpatient cohort in the United States
Authors: Eric Sanfilippo, Sneha Iyer, Nisha Patel, Jonathan I Silverberg
Journal: British Journal of Dermatology (2023)

Abstract Previous population-based studies in the USA found racial and ethnic differences of atopic dermatitis (AD) severity and treatment patterns. It is unclear whether these differences are from differences of disease characteristics or disparities. This study aims to examine racial and ethnic differences in severity and treatment patterns in a diverse outpatient patient cohort of patients with AD (n = 833). A retrospective observational study was performed of patients with physician-diagnosed atopic AD from a large metropolitan tertiary care medical center. Medical records were reviewed for race, ethnicity, disease severity and use of therapies from 10/01/2015-10/1/2021. Atopic dermatitis cases were identified using Hanifin–Rajka criteria. Chi-square or Fisher’s exact tests or were used to assess associations of race and ethnicity with AD severity. Generalized linear models were used to assess interactions of race or ethnicity with gender or age as predictors of individual treatments. There were no significant associations of body surface area (BSA; Fisher’s exact test, P = 0.19 and P = 0.44) or physician’s global assessment (PGA; P = 0.63 and P = 0.57) with race or ethnicity; nor interactions of race/ethnicity with gender or age as predictors of BSA or PGA. Asian and multiracial/other patients were more likely than White or Black patients to use topical calcineurin inhibitors (Chi-square, P = 0.01). Dupilumab use differed by race (Multiracial/other = 35.0%; White = 20.1%; Asian = 15.7%; Black = 13.6%; Chi-square, P = 0.03), but not ethnicity (P = 0.88). Use of oral corticosteroids (Chi-square, P = 0.74), immunosuppressants (P = 0.98) or GABAergics (P = 0.16), or NBUVB (P = 0.42) did not differ by race. There were no statistical interactions of race or ethnicity with gender or age as predictors of treatment use. This study demonstrates that AD severity and specific treatments did not differ overall between racial and ethnic groups in this diverse urban academic cohort.